The polymer additives (PAs) which may migrate from the packaging materials are of concern to manufacturers and suppliers of containers for the heavily regulated pharmaceutical, food and medical device industries. Due to these regulations packaging material manufacturers are directed to control and monitor their products to ensure that no harmful additives are used, which could migrate from these products and cause injuries to the health of the consumers.
Certain rules promulgated by the U.S. Food and Drug Administration mandate the need for adequate information related to packaging materials. An FDA rule, currently in force, states a drug is deemed to be adulterated “if its container is composed, in whole or in part, of any poisonous or deleterious substance which may render the contents injurious to health . . . .” Under this rule, in certain instances, the FDA may require a quantitative extraction profile be obtained for the packaging materials used so as to identify and quantify each detectable substance that may migrate from the packaging materials to their food or drug contents.
The current methods for obtaining a qualitative or quantitative extraction profile include HPLC (high performance or pressure liquid chromatography) and GC (gas chromatography). However, there are shortcomings associated with each of these methods. For example, the GC methods only detect volatile compounds and non-volatile compounds require derivatization prior to a GC analysis, which is burdensome, expensive and time-consuming. In LC methods, although no sample derivatization is required, the typical run time of a sample on an HPLC instrument is about 25 minutes; which has recently been reduced to about 10 minutes by using a UHPLC (ultrahigh performance or pressure chromatography) instrument. However, there are several disadvantages to using HPLC and UHPLC, one of which is their using of toxic organic solvents as mobile phase and generating toxic waste, which is expensive to purchase and dispose of.
The use of non-toxic Supercritical CO2 (SC-CO2) as an alternative to organic solvents as the mobile phase has resulted in the advent of supercritical fluid chromatography (SFC) which embraces many of the features of liquid and gas chromatography. Theoretically, SC-CO2 provides a low viscosity mobile phase that achieves higher diffusion rates and enhanced mass transfer over the solvents used in HPLC. However, the current SFC instruments (which are mainly retooled HPLCs) and methods have many limitations including, for example, long sample run time, inaccurate or imprecise control over the mobile phase density and composition, inability to reliably deliver modifiers at low amounts (<5% of liquid CO2), susceptibility to system pressure fluctuations and sample backflow, baseline noise, sample carryover, and lack of robustness, which prevent users from rapidly obtaining reproducible results.
Therefore, there still remains a need for a more improved chromatography system and method that can overcome the above limitations and allow for a rapid and robust analysis of the polymer additives extractable and/or leachable from packaging materials or implantable medical devices.